tbuckley/cabot-search huggingface dataset:
Berzosertib Plus Topotecan vs Topotecan Alone in Patients With Relapsed Small Cell Lung Cancer
Authors: Nobuyuki Takahashi, Zhonglin Hao, Liza C. Villaruz, Jun Zhang, Jimmy Ruiz, W. Jeffrey Petty, Hirva Mamdani, Jonathan W. Riess, Jorge Nieva, Jose M. Pachecho, Alexander D. Fuld, Elaine Shum, Aman Chauhan, Samantha Nichols, Hirity Shimellis, Jessie McGlone, Linda Sciuto, Danielle Pinkiert, Chante Graham, Meenakshi Shelat, Robbie Kattappuram, Melissa Abel, Brett Schroeder, Deep Upadhyay, Manan Krishnamurthy, Ajit Kumar Sharma, Rajesh Kumar, Justin Malin, Christopher W. Schultz, Shubhank Goyal, Christophe E. Redon, Yves Pommier, Mirit I. Aladjem, Steven D. Gore, Seth M. Steinberg, Rasa Vilimas, Parth Desai, Anish Thomas
Journal: JAMA Oncology (2023)

Patients with relapsed small cell lung cancer (SCLC), a high replication stress tumor, have poor prognoses and few therapeutic options. A phase 2 study showed antitumor activity with the addition of the ataxia telangiectasia and Rad3-related kinase inhibitor berzosertib to topotecan.
A randomized, double‐blind, placebo‐controlled trial with mannan‐conjugated birch pollen allergoids
Authors: Ralph Mösges, Christoph Zeyen, Esther Raskopf, Cengizhan Acikel, Hacer Sahin, Silke Allekotte, Mandy Cuevas, Mohamed H. Shamji, José Luis Subiza, Miguel Casanovas
Journal: Allergy (2023)

Abstract Background There is still great need to develop new strategies to improve the efficacy of allergen immunotherapies with optimal safety standards for patients. A new promising approach is to couple allergoids to mannan. The objective of this phase IIa/IIb study was to identify the optimal dose of mannan‐conjugated birch pollen allergoids for the short‐course treatment of birch pollen–induced allergic rhinoconjunctivitis. Methods For this prospective, randomized, double‐blind, placebo‐controlled, dose‐finding study, 246 birch pollen–allergic adults received 0.5 mL placebo or 1000, 3000 or 10,000 mTU/mL of mannan‐conjugated birch pollen allergoids at five pre‐seasonal visits. Efficacy was assessed by comparing allergic rhinoconjunctivitis symptoms and use of anti‐allergic medication during the peak of the birch pollen season 2020. Immunologic, tolerability and safety effects were also analysed. Results The highest dose of mannan‐conjugated birch pollen allergoids reduced the combined symptom and medication score during the peak birch pollen season by a median of 24.7% compared to placebo. The production of Bet v 1 specific IgG4 significantly increased in a dose‐dependent manner (3.6‐ and 4.5‐fold) in the 3000 and 10,000 mTU/mL groups. The Bet v 1 specific IgE/IgG4 ratio was also strongly reduced (up to −70%). No fatalities nor serious adverse events were reported, and no adrenaline was used. In total, four systemic reactions occurred (two grade I and two grade II). Conclusion All doses of mannan‐conjugated birch pollen allergoids can be considered as safe. Since the application of 10,000 mTU/mL resulted in the highest efficacy, this dose qualifies for further investigation.
The Burden of Lung Cancer in Women Compared With Men in the US
Authors: Ahmedin Jemal, Elizabeth J. Schafer, Hyuna Sung, Priti Bandi, Tyler Kratzer, Farhad Islami, Rebecca L. Siegel
Journal: JAMA Oncology (2023)

This cross-sectional study examines the incidence rates of lung cancer in women compared with men from 2000 to 2019.
Schwann cell–derived extracellular vesicles as a potential therapy for retinal ganglion cell degeneration
Authors: Senmiao Zhu, Lili Chen, Min Wang, Jing Zhang, Gang Chen, Yinghao Yao, Shihan Song, Tong Li, Shenglan Xu, Zhonghao Yu, Bingyan Shen, Duogang Xu, Zai-Long Chi, Wencan Wu
Journal: Journal of Controlled Release (2023)

Optic neuropathy is the leading cause of irreversible blindness and is characterized by progressive degeneration of retinal ganglion cells (RGCs). Several studies have demonstrated that transplantation of Schwann cells (SCs) is a promising candidate therapy for optic neuropathy and that intravitreally transplanted cells exert their effect via paracrine actions. Extracellular vesicle (EV)-based therapies are increasingly recognized as a potential strategy for cell replacement therapy. In this study, we aimed to investigate the neuroprotective and regenerative effects of SC-EVs following optic nerve injury. We found that SC-EVs were internalized by RGCs in vitro and in vivo without any transfection reagents. Intriguingly, SC-EVs significantly enhanced the survival and axonal growth of primary RGCs in a coculture system. In a rat optic nerve crush model, SC-EVs mitigated RGC degeneration, prevented RGC loss, and preserved the thickness of the ganglion cell complex, as demonstrated by the statistically significant improvement in RGC counts and thickness measurements. Mechanistically, SC-EVs activated the cAMP-response element binding protein (CREB) signaling pathway and regulated reactive gliosis in ONC rats, which is crucial for RGC protection and axonal regeneration. These findings provide novel insights into the neuroprotective and regenerative properties of SC-EVs, suggesting their potential as a cell-free therapeutic strategy and natural biomaterials for neurodegenerative diseases of the central nervous system.
FBXO38 regulates macrophage polarization to control the development of cancer and colitis
Authors: Xin Zheng, Qi Jiang, Mingshun Han, Fenfen Ye, Mingchang Wang, Ying Qiu, Jialu Wang, Minxia Gao, Fajian Hou, Hongyan Wang
Journal: Cellular and Molecular Immunology (2023)
Ion incorporation into bone grafting materials
Authors: Qin Zhao, Yueqi Ni, Hongjiang Wei, Yiling Duan, Jingqiu Chen, Qi Xiao, Jie Gao, Yiqian Yu, Yu Cui, Simin Ouyang, Richard J. Miron, Yufeng Zhang, Chengtie Wu
Journal: Periodontology 2000 (2023)

The use of biomaterials in regenerative medicine has expanded to treat various disorders caused by trauma or disease in orthopedics and dentistry. However, the treatment of large and complex bone defects presents a challenge, leading to a pressing need for optimized biomaterials for bone repair. Recent advances in chemical sciences have enabled the incorporation of therapeutic ions into bone grafts to enhance their performance. These ions, such as strontium (for bone regeneration/osteoporosis), copper (for angiogenesis), boron (for bone growth), iron (for chemotaxis), cobalt (for B12 synthesis), lithium (for osteogenesis/cementogenesis), silver (for antibacterial resistance), and magnesium (for bone and cartilage regeneration), among others (e.g., zinc, sodium, and silica), have been studied extensively. This review aims to provide a comprehensive overview of current knowledge and recent developments in ion incorporation into biomaterials for bone and periodontal tissue repair. It also discusses recently developed biomaterials from a basic design and clinical application perspective. Additionally, the review highlights the importance of precise ion introduction into biomaterials to address existing limitations and challenges in combination therapies. Future prospects and opportunities for the development and optimization of biomaterials for bone tissue engineering are emphasized.
Is there room for another anti-interleukin-17 treatment in the crowded psoriasis therapeutic landscape?
Authors: Christina Bergqvist
Journal: British Journal of Dermatology (2023)

Journal Article Accepted manuscript Is there room for another Anti-IL-17 in the Crowded Psoriasis Therapeutic Landscape? Get access Christina Bergqvist Christina Bergqvist Department of Dermatology, Henri Mondor Hospital, Créteil, France Email:Christina.Bergqvist@aphp.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad383, https://doi.org/10.1093/bjd/ljad383 Published: 12 October 2023 Article history Received: 23 September 2023 Accepted: 11 October 2023 Published: 12 October 2023
Toll-Like Receptor 4 Agonist Injection With Concurrent Radiotherapy in Patients With Metastatic Soft Tissue Sarcoma
Authors: Yongwoo David Seo, Hailing Lu, Graeme Black, Kimberly Smythe, Yuexin Yu, Cynthia Hsu, Juliana Ng, Pedro Hermida de Viveiros, E. Houston Warren, Brett A. Schroeder, Ryan B. O’Malley, Lee D. Cranmer, Elizabeth T. Loggers, Michael J. Wagner, Lynn Bonham, Venu G. Pillarisetty, Gabrielle Kane, Peter Berglund, Frank J. Hsu, Xinlei Mi, Borislav A. Alexiev, Robert H. Pierce, Stanley R. Riddell, Robin L. Jones, Jan ter Meulen, Edward Y. Kim, Seth M. Pollack
Journal: JAMA Oncology (2023)

Metastatic soft tissue sarcomas (STSs) have limited systemic therapy options, and immunomodulation has not yet meaningfully improved outcomes. Intratumoral (IT) injection of the toll-like receptor 4 (TLR4) agonist glycopyranosyl lipid A in stable-emulsion formulation (GLA-SE) has been studied as immunotherapy in other contexts.To evaluate the safety, efficacy, and immunomodulatory effects of IT GLA-SE with concurrent radiotherapy in patients with metastatic STS with injectable lesions.This phase 1 nonrandomized controlled trial of patients with STS was performed at a single academic sarcoma specialty center from November 17, 2014, to March 16, 2016. Data analysis was performed from August 2016 to September 2022.Two doses of IT GLA-SE (5 μg and 10 μg for 8 weekly doses) were tested for safety in combination with concurrent radiotherapy of the injected lesion.Primary end points were safety and tolerability. Secondary and exploratory end points included local response rates as well as measurement of antitumor immunity with immunohistochemistry and T-cell receptor (TCR) sequencing of tumor-infiltrating and circulating lymphocytes.Twelve patients (median [range] age, 65 [34-78] years; 8 [67%] female) were treated across the 2 dose cohorts. Intratumoral GLA-SE was well tolerated, with only 1 patient (8%) experiencing a grade 2 adverse event. All patients achieved local control of the injected lesion after 8 doses, with 1 patient having complete regression (mean regression, -25%; range, -100% to 4%). In patients with durable local response, there were detectable increases in tumor-infiltrating lymphocytes. In 1 patient (target lesion -39% at 259 days of follow-up), TCR sequencing revealed expansion of preexisting and de novo clonotypes, with convergence of numerous rearrangements coding for the same binding sequence (suggestive of clonal convergence to antitumor targets). Single-cell sequencing identified these same expanded TCR clones in peripheral blood after treatment; these T cells had markedly enhanced Tbet expression, suggesting TH1 phenotype.In this nonrandomized controlled trial, IT GLA-SE with concurrent radiotherapy was well tolerated and provided more durable local control than radiotherapy alone. Patients with durable local response demonstrated enhanced IT T-cell clonal expansion, with matched expansion of these clonotypes in the circulation. Additional studies evaluating synergism of IT GLA-SE and radiotherapy with systemic immune modulation are warranted.ClinicalTrials.gov Identifier: NCT02180698.
Are Cancer Biosimilars Similar and Significant Enough to Deserve More Attention?
Authors: Chen Mao, Mengfeng Li
Journal: JAMA Network Open (2023)

Xingxian Luo, PhD; Xin Du, MSc; Zhuangqi Li, MSc; Jingwen Liu, MSc; Xufeng Lv, MSc; Haoran Li, BS; Qixiang Guo, MSc; Cen Wang, PhD; Xuecai Xue, MSc; Kaidi Le, MSc; Xiaomeng Jiang, MSc; Lin Huang, PhD; Yue Yang, PhD
B cell diversification in gut-associated lymphoid tissues: From birds to humans
Authors: Jean-Claude Weill, Sandra Weller, Claude-Agnès Reynaud
Journal: The Journal of Experimental Medicine (2023)

Several species generate their preimmune repertoire in gut-associated lymphoid tissues (GALT), compensating a reduced germline V gene repertoire by post-rearrangement diversification mechanisms (gene conversion and/or somatic hypermutation) in these environments that act as primary lymphoid organs. We summarize here these processes for three different species (chickens, sheep, and rabbits) and further discuss the analogous process that T-independent B cell responses in humans represent: we indeed recently showed that response against bacterial polysaccharides mobilize marginal zone B cells that prediversified against gut antigens. While the initial diversification strategy differs in these two cases, i.e., repertoire formation driven by gut-derived mitotic signals vs. response against gut antigens, the common feature of these two processes is the mobilization of a B cell compartment prediversified in GALT for immune responses against distinct systemic antigens.
Muscle Mass and Serum Creatinine Concentration by Race and Ethnicity among Hemodialysis Patients
Authors: Cynthia Delgado, Neil R. Powe, Glenn M. Chertow, Barbara Grimes, Kirsten L. Johansen
Journal: Journal of the American Society of Nephrology (2023)

Significance Statement Serum creatinine is a product of skeletal muscle metabolism. Differences in serum creatinine concentration between Black and non-Black individuals have been attributed to differences in muscle mass but have not been thoroughly examined. Furthermore, other race and ethnic groups have not been considered. If differences in body composition explain differences in serum concentration by race or ethnicity, then estimates of body composition could be used in eGFR equations rather than race. Adjustment for intracellular water (ICW) as a proxy of muscle mass among patients with kidney failure in whom creatinine clearance should minimally influence serum concentration does not explain race- and ethnicity-dependent differences. Background Differences in serum creatinine concentration among groups defined by race and ethnicity have been ascribed to differences in muscle mass. We examined differences in serum creatinine by race and ethnicity in a cohort of patients receiving hemodialysis in whom creatinine elimination by the kidney should have little or no effect on serum creatinine concentration and considered whether these differences persisted after adjustment for proxies of muscle mass. Methods We analyzed data from 501 participants in the A Cohort Study to Investigate the Value of Exercise in ESKD/Analyses Designed to Investigate the Paradox of Obesity and Survival in ESKD study who had been receiving hemodialysis for &gt;1 year. We examined the independent associations among race and ethnicity (Black, Asian, non-Hispanic White, and Hispanic), serum creatinine, and ICW (L/m 2 ), a proxy for muscle mass, derived by whole-body multifrequency bioimpedance spectroscopy, using multivariable linear regression with adjustment for several demographic, clinical, and laboratory characteristics. We examined the association of race and ethnicity with serum creatinine concentration with and without adjustment for ICW. Results Black, Asian, and Hispanic patients had higher serum creatinine concentrations (+1.68 mg/dl [95% confidence interval (CI), 1.09 to 2.27], +1.61 mg/dl [95% CI, 0.90 to 2.32], and +0.83 [95% CI, 0.08 to 1.57], respectively) than non-Hispanic White patients. Overall, ICW was associated with serum creatinine concentration (0.26 mg/dl per L/m 2 ICW; 95% CI, 0.006 to 0.51) but was not statistically significantly different by race and ethnicity. Black, Asian, and Hispanic race and ethnicity remained significantly associated with serum creatinine concentration after adjustment for ICW. Conclusion Among patients receiving dialysis, serum creatinine was higher in Black, Asian, and Hispanic patients than in non-Hispanic White patients. Differences in ICW did not explain the differences in serum creatinine concentration across race groups.
The Apolipoprotein E neutralizing antibody inhibits SARS‐CoV‐2 infection by blocking cellular entry of lipoviral particles
Authors: Qi Cui, Arjit Vijey Jeyachandran, Gustavo Garcia, Chao Qin, Yu Zhou, Mingzi Zhang, Cheng Wang, Guihua Sun, Wei Liu, Tao Zhou, Lizhao Feng, Chance Palmer, Zhuo Li, Adam Aziz, Brigitte N. Gomperts, Pinghui Feng, Vaithilingaraja Arumugaswami, Yanhong Shi
Journal: MedComm (2023)

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is the causal agent for coronavirus disease 2019 (COVID‐19). Although vaccines have helped to prevent uncontrolled viral spreading, our understanding of the fundamental biology of SARS‐CoV‐2 infection remains insufficient, which hinders effective therapeutic development. Here, we found that Apolipoprotein E (ApoE), a lipid binding protein, is hijacked by SARS‐CoV‐2 for infection. Preincubation of SARS‐CoV‐2 with a neutralizing antibody specific to ApoE led to inhibition of SARS‐CoV‐2 infection. The ApoE neutralizing antibody efficiently blocked SARS‐CoV‐2 infection of human iPSC‐derived astrocytes and air–liquid interface organoid models in addition to human ACE2‐expressing HEK293T cells and Calu‐3 lung cells. ApoE mediates SARS‐CoV‐2 entry through binding to its cellular receptors such as the low density lipoprotein receptor (LDLR). LDLR knockout or ApoE mutations at the receptor binding domain or an ApoE mimetic peptide reduced SARS‐CoV‐2 infection. Furthermore, we detected strong membrane LDLR expression on SARS‐CoV‐2 Spike‐positive cells in human lung tissues, whereas no or low ACE2 expression was detected. This study provides a new paradigm for SARS‐CoV‐2 cellular entry through binding of ApoE on the lipoviral particles to host cell receptor(s). Moreover, this study suggests that ApoE neutralizing antibodies are promising antiviral therapies for COVID‐19 by blocking entry of both parental virus and variants of concern.
Environmental violence: a tool for planetary health research
Authors: Richard Marcantonio, Agustín Fuentes
Journal: The Lancet Planetary Health (2023)

From climate change to toxic pollution and the interactive effects of multiple pollution streams, human health is under siege. Human-produced environmental risks to health and wellbeing are high and contributing to patterns of global morbidity, mortality, economic inequality, displacement, and insecurity. The implications of human-produced environmental harms to global health are complex just as are their causes. The concept of environmental violence offers a potentially robust frame for engaging this issue. We argue that a more specified and structured framework and definition of environmental violence—focusing on human-produced harms by way of pollution emissions—is both timely and beneficial for engaging the complexities of global public health. To clarify why and how this is the case, we review the literature for publications that use the term environmental violence and we subsequently propose a specific definition focused on human-produced pollution along with a framework for tracking and analysing environmental violence and its constituent components. Finally, we discuss the potential value of our framework for research and policy making regarding human health.
Clinical characteristics and prognosis of patients with isolated cardiac sarcoidosis: Insights from the <scp>ILLUMINATE‐CS</scp> study
Authors: Daichi Maeda, Yuya Matsue, Taishi Dotare, Tsutomu Sunayama, Takashi Iso, Kenji Yoshioka, Takeru Nabeta, Yoshihisa Naruse, Takeshi Kitai, Tatsunori Taniguchi, Hidekazu Tanaka, Takahiro Okumura, Yuichi Baba, Tohru Minamino
Journal: European Journal of Heart Failure (2023)
3D printing for bone regeneration: challenges and opportunities for achieving predictability
Authors: Saso Ivanovski, Omar Breik, Danilo Carluccio, Jamil Alayan, Ruben Staples, Cedryck Vaquette
Journal: Periodontology 2000 (2023)

Abstract 3D printing offers attractive opportunities for large‐volume bone regeneration in the oro‐dental and craniofacial regions. This is enabled by the development of CAD‐CAM technologies that support the design and manufacturing of anatomically accurate meshes and scaffolds. This review describes the main 3D‐printing technologies utilized for the fabrication of these patient‐matched devices, and reports on their pre‐clinical and clinical performance including the occurrence of complications for vertical bone augmentation and craniofacial applications. Furthermore, the regulatory pathway for approval of these devices is discussed, highlighting the main hurdles and obstacles. Finally, the review elaborates on a variety of strategies for increasing bone regeneration capacity and explores the future of 4D bioprinting and biodegradable metal 3D printing.
Alternative therapies against Mycobacterium abscessus infections
Authors: Ivana Palucci, Giovanni Delogu
Journal: Clinical Microbiology and Infection (2023)

BackgroundMycobacterium abscessus (Mab) is considered as the most pathogenic rapid-growing mycobacteria in humans, causing pulmonary and extra-pulmonary diseases, especially in patients with cystic fibrosis. Mab shows intrinsic and acquired resistance to many drugs, leaving limited treatment options that lead to a generally poor prognosis. The standard therapeutic regimen last for more than 6 months and consists of a drug cocktail that ideally includes a macrolide and amikacin. Yet, toxicity and efficacy are suboptimal due also to the high toxicity. There is a need to introduce innovative and out-of-the-box approaches to improve treatments.ObjectivesIn this narrative review, we summarize the recent research on the alternative strategies proposed and discuss the importance of using appropriate experimental assays to assess their activity.SourcesIncluded articles were identified by searching PubMed and MEDLINE until June 2023. The search terms were 'Mycobacterium abscessus', 'antimicrobial', and 'alternative therapies'. Additional relevant references were obtained from articles retrieved from the primary search.ContentTherapies against Mab including host directed therapies, repurposed drugs, phage therapy, anti-virulence strategies, essential oils, and inhalation therapies.ImplicationsAlternative treatments may represent a valid tool to cope the burden of antimicrobial resistance in Mab-caused diseases.
Circulating Tumor HPV DNA for Surveillance of HPV-Positive Oropharyngeal Squamous Cell Carcinoma
Authors: Krystle A. Lang Kuhs, J. Chad Brenner, F. Chris Holsinger, Eleni M. Rettig
Journal: JAMA Oncology (2023)

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma has an overall favorable prognosis, yet a subset of patients will experience devastating disease recurrence. Current surveillance standards for detection of recurrent disease are imperfect. There is growing interest in improving detection of recurrent disease through the use of plasma-based assays able to detect circulating tumor HPV DNA.Although most circulating tumor HPV DNA assays remain in the research domain, the circulating tumor tissue-modified viral HPV DNA assay became commercially available in the United States in early 2020 and has been increasingly used in the clinical setting. With the rapidly increasing incidence of HPV-positive oropharyngeal squamous cell carcinoma and concomitant expansion of biomarker capabilities for this disease, it is critical to reexamine current posttreatment surveillance practices and to determine whether emerging technologies may be used to improve outcomes for a growing survivor population. However, caution is advised; it is not yet known whether biomarker-based surveillance is truly beneficial, and as is true with any intervention, it has the capacity to cause harm.Using Margaret Pepe's classic 5 phases of biomarker development for early detection of cancer as a framework, this article reviews the current state of knowledge, highlights existing knowledge gaps, and suggests research that should be prioritized to understand the association between biomarker-based surveillance and patient outcomes. Specific attention is paid to the commercially available tumor tissue-modified viral HPV DNA assay, given its increasing clinical use. This review may serve as a road map for future research and a guide for clinicians considering its adoption in practice. Enrollment of patients into clinical trials incorporating biomarker-based surveillance should be prioritized.